Prof.Dr.Yıldız CamcıoğluİÜ.Cerahpaşa Tıp Fakültesi

Çocuk Sağlığı ve Hastalıkları ABD

Enfeksiyon Hastalıkları, Klinik İmmünoloji ve Allerji Bilim Dalı

Principles of Vaccination

• Protection from infectious disease

• Usually indicated by the presence of antibody

• Very specific to a single antigen

Immunity

1990-2001 Infectious Diseases(CDC)

varicella 48164 0 100

Diptheria 175885 2 > 99

Pertussis 147271 7560 95

Tetanus 1314 37 97

Polio 16319 0 100

Measles 503282 116 > 99

Mumps 152209 266 > 99

Rubella 47745 23 > 99

Hib 20000 181 > 99

illness 1990-99 morbidity 2001 morbidity % reduction

What is Vaccine  ?• Vaccinations are supposed to confer immunity • Standard manufacture uses a bacterial or viral antigen • Bacterium or virus, which may be killed, generally with

formol or heat may be living but attenuated.• Bacterial vaccines can contain All of the bacterium (killed by heat ;whooping-cough

vaccine) or can be acellular (only antigenic fragments). • Diphtheria and tetanus vaccines are “anatoxins”; they

contain only the toxin (attenuated) produced by the bacteria and supposed to be responsible for the disease

• The attenuation by rapid passage in a culture (BCG by 230 passages in potatoes mixed with beef bile; or measles by 85 passages in chicken fibroblasts)

Principles of Vaccination

• Protection produced by the person's own immune system

• Usually permanent

• Protection transferred from another person or animal as antibody

• Temporary protection that wanes with time

Active Immunity

Passive Immunity

A2

Principles of Vaccination

• A live or inactivated substance capable of producing an immune response

Single constituent,e.g.,, polysaccharide or tetanus, diphteria)

Complex constituent(live viruses , killed pertusssis bacteria)

• Protein molecules (immunoglobulin) produced by B lymphocytes to help eliminate an antigen

Antigen

Antibody

Passive Immunity

• Transfer of antibody produced by one human or other animal to another

• Transplacental most important source in infancy

• Temporary protection

Sources of Passive Immunity

• Almost all blood or blood products

• Homologous pooled human antibody (immune globulin)

• Homologous human hyperimmune globulin

• Heterologous hyperimmune serum (antitoxin)

Vaccination

• Active immunity produced by vaccine

• Immunity and immunologic memory similar to natural infection but without risk of disease

Vaccines

Effective vaccines are: • Safe • Protective for sustained period • Induce neutralising antibody • In addition they should be: • Biologically stable • Cheap to produce • Easy to administer

Classification of Vaccines

Currently available vaccines are either:

• Live (attenuated)

• Killed or Inactivated

• Fractionated

• Recombinant Live attenuated

Inactivated Vaccines

• virus• bacteria

• protein-based– subunit– toxoid

• polysaccharide-based– pure– conjugate

Whole

Fractional

Live Attenuated Vaccines

• Attenuated (weakened) form of the "wild" virus or bacteria

• Must replicate to be effective

• Immune response similar to natural infection

• Usually effective with one dose*

*except those administered orally

Live Attenuated Vaccines

• Severe reactions possible

• Interference from circulating antibody

• Unstable

Live Attenuated Vaccines

• Viral measles, mumps,rubella, vaccinia,varicella, yellow fever,influenza, (oral polio)(rotavirus)

• Bacterial BCG, oral typhoid

Vaccines in (parenthesis) are not available in the United States.

Inactivated Vaccines

• Cannot replicate

• Minimal interference from circulating antibody

• Generally not as effective as live vaccines

• Generally require 3-5 doses

• Immune response mostly humoral

• Antibody titer diminishes with time

Inactivated Vaccines

• Viral polio, hepatitis A, rabies, influenza

• Bacterial pertussis, typhoid cholera, plague

Whole cell vaccines

Vaccines in (parenthesis) are not available in the United States.

Inactivated Vaccines

• Subunit hepatitis B, influenza, acellular pertussis, Lyme

•

• Toxoid diphtheria, tetanus

Fractional vaccines

Polysaccharide Vaccines

• pneumococcal

• meningococcal

• Salmonella Typhi (Vi)

• Haemophilus influenzae type b

• pneumococcal

Pure polysaccharide

Conjugate polysaccharide

Pure Polysaccharide Vaccines

• Not consistently immunogenic in children <2 years of age

• No booster response

• Antibody with less functional activity

• Immunogenicity improved by conjugation

Immunological Principles of Vaccination

• Vaccination is intended to provide long-term protection after its administration

• Effector T- and B-cells last only a few days,

so the prime requisite of any vaccine is to generate immunological memory.

Successful Vaccines• Activate antigen-presenting cells to initiate antigen

processing and produce cytokines • Activate both T and B cells to give a high yield of

memory cells • Generate Th and Tc cells to several epitopes, to

overcome the variation in the immune response in the population due to MHC polymorphism

• Enable the persistence of antigen, probably on follicular dendritic cells in lymphoid tissue, to elicit continued production of antibody from B cells.

• Whole organism vaccines tend to have these abilities. Subunit vaccines can be enhanced to produce these results by the use of adjuvants, such as alum.

Content of Vaccines

Component Functions • Prezervatives Prevent bacterial growth • Stabilizers Stabilize the antigen • Antibiotics Neomycin, Streptomycin• Adjuvants Enhances immunogenecity Aluminum hydroxide• Suspending fluids Sterile water or saline

Complex fluids (egg yolk antigen,

substances in tissue culture, serum proteins)

Preservatives• Tiomersal ; DT, dT, TT, İnfluenzae

Pneumococcal polysaccharide(Wyett) • 2-phenoxietanol ve formaldehide; IPV• Phenol Tifo Vi,

Pneumococcal polysaccharide (pasteur) • Benzetonium chlorur(femerol); Şarbon• 2-phenoxyetanol; DBaT (Infanrix, GSK)

Hepatitis A (Havrix, GSK)

Hepatitis A/B(Twinrix, GSK)

Lyme (Lymerix, GSK)

Vaccines 1• Attenuated Vaccines; • Viral : Polio (Sabin), Measles, Rubella, Mumps,

Varicella, Rotavirus, Sarı humma

Bacterial; BCG

Vaccines 2• Toxoid: Exotoxin inactivated by phormaldehide

Tetanus, Diphteria • Subunite vaccines: Influenzae, Hepatitis B, Acellular

pertussis• Inactivated whole cell : inactiveted by phormaldehide Polio (Salk), Influenzae , Rabies, Hepatitis A,

Pertussis, Typhi, Cholera, Plaque• Pure polysaccharide (TI); S.pneumoniae

N.Meningitidis• Conjugated-polysaccharide;TD antigen; Hib,

S.pneumoniae Polysaccharides

proteins conjugatedTetanus, OMP, Diphteria

• Hepatitis B surface antigen gene

• Produce in Maya cells

• Purification of recombinant strain

• Immune response

Recombinant(syntetic) vaccine

Attenuated and inactivated vaccine

Properties Attenuated Vaccine Inactivated Vaccine

Preparation Virulent strain, various culture medium, long passages

Pathogen, inactivated by chemicals or gamma radiation

Booster Just one More than one

Stabilization NOT GOOD BETTER stabilized

Immune response Humoral and cellular

Humoral

Adjuvant name

Compositions Mechanism of action

Freund’s incomplete adjuvant

Oil-in- emulsion Delayed release of antigen,

Enhanced uptake by macrophages

Freund’s complete adjuvant

Oil-in- water with

dead Mycobacteria

Delayed release of antigen,Enhanced uptake by macrophages Induction of co-stimulators in macrophages

Freund’s adjuvant

With MDP

Oil-in- water with

Muramyldipeptid

Delayed release of antigen,

Enhanced uptake by macrophagesInduction of co-stimulators in macrophages

Alum Aluminum Hidroxide gel

Delayed release of antigen,

Enhanced uptake by macrophages

Alum+B.pertussis Aluminum Hidroxide gel with

Killed B.pertussis

Delayed release of antigen,Enhanced uptake by macrophages Induction of co-stimulators in macrophages

Immun stimulatory complexes(ISCOM)

Matrix of lipid micelles containing Viral proteins

Delivers antigen to cytosol

İnduction of Cytotoxic T cells

T Independent antigens: ( TI)TI-1 E.coli LPSTI-2 Pneumoccus polysaccaride H.influenza tip b (Hib-prp) Meningococcus polysaccaride T Dependent antigens: (TD)

•Tetanus toxoid•Dipheriae toxoid•Influenzae vaccine•Inactive polio vaccine(Salk)

Ministry of Health-Immunization Schedule 2013TURKEY

Birth1.

month2.

month4.

month6.

month12.

month18.

month24.

month6-7

years13-14years

Hep-B 1.dose 2.dose 3.doseBCG (Tb vaccine)

1.dose

DTaP-IPV-Hib - 1.dose 2.dose 3.dose 4.dose

Pneumococcal ConjugatedVaccine (PCV)

1.dose 2.dose 3.dose 4.dose

MMR 1.dose 2.dose

DTaP-IPV 1.doseOral Polio vaccine(OPV)

1.dose 2.dose

Td(Tetanus,adult dose diphteria

1.dose

Hep-A 1.dose 2.dose

Varicella 1.dose

• DTaP-IPV-Hib: Diphtheria/Tetanus Toxoids/Acellular Pertussis/Inactivated Polio Vaccine (Diphteria, acellular Pertussis, Tetanus, Inactivated Polio vaccine, Hemofilus influenzae type b vaccinePCV: Pneumococcal Conjugated VaccineMMR :Measles, Mumps, RubellaDTaP-IPA: Diphtheria/Tetanus Toxoids/Acellular Pertussis/Inactivated Polio Vaccine

• OPA: Oral Polio VaccineTd:Tetanus and adult type diphteriaB:Booster

Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for Persons Aged 0 Through 18 Years —

United States, 2013

<6 years of age, Never vaccinated previously

• First day DaBT-IPA-Hib, Hep B1, PPD• 2 days later MMR1, BCG• 2 months later DaBT-IPA-Hib, * • At least 8 months later DaBT-IPA-Hib, Hep B3, OPA

>6 years of age, Never vaccinated previously

• First Day;

Td1, OPA1, Hep B1, MMR

• 1 month later

Td2, OPA2, Hep B2, MMR

• At least 8 months later Td3, OPA3, Hep B3

Vaccination at School• At class 6

OPA-3, MMR-Booster, Td-1 • At class 8

Td-2

Rubella (Vaccine introduced in 2007, Born children in 2007 are not vaccinated. They are the cohort to be vaccinated)

Hepatitis B; 3 doses, at intervals 0-1-4

(Vaccine introduced in 1998 , Born children in 1998 are not vaccinated, They are the cohort to be vaccinated)

Vaccination scheduled for Adolecent

Hepatitis B; No vaccination previously 0,1, 6

MMR; 2 doses before 12 years of age, once who has not vaccinated previosly

Varicella; Once for 11-12 years of age

2 doses, 1-2 months interval, after 13 years of age

Meningoccoccus; Once for the adolecents at high risksuch as dormitories

Hepatitis A; 0 and 6

HPV ; 0, 2, 6

Catch-up vaccination in USA• Persons aged 7 through 10 years who are not fully immunized with the childhood DTaP vaccine series, should receive Tdap vaccine as the first dose in the catch-up series; if additional doses are needed, use Td vaccine. For these children, an adolescent Tdap vaccine should not be given.

• Persons aged 11 through 18 years who have not received Tdap vaccine should receive a dose followed by tetanus and diphtheria toxoids (Td) booster doses every 10 years thereafter.

• An inadvertent dose of DTaP vaccine administered to children aged 7 through 10 years can count as part of the catch-up series. This dose can count as the adolescent Tdap dose, or the child can

later receive a Tdap booster dose at age 11–12 years.

These children should not get vaccines• People with minor illnesses, such as a cold, may be

vaccinated• These people should wait: Anyone who is moderately

or severely ill at the time the shot is scheduled should usually wait until they recover before getting vaccine

• Primary or secondary immunodeficiencies• Any one who had a severe unexpected or allergic

reaction to a vaccine should not get another one• Anyone who has ever had a life-threatening allergic

reaction to the antibiotics: neomycin, streptomycin or polymyxin B or Egg should NOT get the vaccine

• Pregnancy, avoid with live vaccines

Schedule for Routine Immunizations• Advisory Committee on Immunization Practices (ACIP),

American Academy of Pediatrics (AAP), American Academy of Family Physicians (AAFP)

• Infants born to HBsAg-negative mothers should receive 2.5 µg of Merck vaccine (Recombivax HBÆ ) or 10 µg of SmithKlineBeecham (SB) vaccine (Engerix-BÆ )

The 2nd dose should be administered greater than or equal to one month after the 1st dose.

• Infants born to HBsAg-positive mothers should receive 0.5 mL hepatitis B immune globulin (HBIG) within 12 hrs

of birth and either 5µg of Merck vaccine (Recombivax HBÆ ) or 10 µg of SB vaccine (Engerix-BÆ ) at a separate site. The 2nd dose is recommended at 1-2 months of age and the 3rd dose at 6 months of age

• DTaP (diphtheria and tetanus toxoids and acellular pertussis vaccine) is the preferred vaccine or equal to 1 dose of whole-cell DTP vaccine.

• Td (tetanus and diphtheria toxoids, adsorbed, for adult use) is recommended at 11-12 yrs of age if at least 5 years have elapsed since the last dose of DTP, DTaP, or DT. Subsequent routine Td boosters are recommended every 10 years.

• H. influenzae type b (Hib) conjugate vaccines are licensed for infant use.

• Two poliovirus vaccines are currently licensed; inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV). – IPV at 2 and 4 mos; OPV at 12-18 months and 4-6

years – IPV at 2, 4, 12-18 months, and 4-6 years – OPV at 2, 4, 6-18 months, and 4-6 years

• IPV is the only poliovirus vaccine recommended for immunocompromised persons and their household contacts

• The first dose of MMR at 12 months of age The 2nd dose of MMR at 4-6 or at 11-12 years of age• Susceptible children may receive Varicella vaccine

(Var) after the 1st birthday. Susceptible persons 13 years of age or older should receive 2 doses at least 1 month apart.